1] Department of Anesthesia, Stanford University School of Medicine, Stanford, California, USA [2] Department of Emergency Medicine, Chonnam National University School of Medicine, Gwangju, South Korea.
J Cereb Blood Flow Metab. 2013 Dec;33(12):1976-82. doi: 10.1038/jcbfm.2013.157. Epub 2013 Sep 4.
MicroRNA (miRNA), miR-181a, is enriched in the brain, and inhibition of miR-181a reduced astrocyte death in vitro and infarct volume after stroke in vivo. This study investigated the role of miR-181a in neuronal injury in vitro and hippocampal neuronal loss in vivo after forebrain ischemia. miR-181a levels were altered by transfection with mimic or antagomir. N2a cells subjected to serum deprivation and oxidative stress showed less cell death when miR-181a was reduced and increased death when miR-181a increased; protection was associated with increased Bcl-2 protein. In contrast, transfected primary neurons did not show altered levels of cell death when miR-181a levels changed. Naive male rats and rats stereotactically infused with miR-181a antagomir or control were subjected to forebrain ischemia and cornus ammonis (CA)1 neuronal survival and protein levels were assessed. Forebrain ischemia increased miR-181a expression and decreased Bcl-2 protein in the hippocampal CA1 region. miR-181a antagomir reduced miR-181a levels, reduced CA1 neuronal loss, increased Bcl-2 protein, and significantly prevented the decrease of glutamate transporter 1. Thus, miR-181a antagomir reduced evidence of astrocyte dysfunction and increased CA1 neuronal survival. miR-181a inhibition is thus a potential target in the setting of forebrain or global cerebral ischemia as well as focal ischemia.
微小 RNA（miRNA），miR-181a，在大脑中富集，抑制 miR-181a 可减少体外星形胶质细胞死亡和体内中风后梗死体积。本研究探讨了 miR-181a 在体外神经元损伤和体内海马神经元丢失中的作用。通过转染模拟物或反义寡核苷酸来改变 miR-181a 的水平。血清剥夺和氧化应激后，N2a 细胞中 miR-181a 减少时细胞死亡减少，而 miR-181a 增加时细胞死亡增加；保护与 Bcl-2 蛋白增加有关。相比之下，转染的原代神经元在 miR-181a 水平变化时并未显示出细胞死亡水平的改变。未处理的雄性大鼠和立体定向注射 miR-181a 反义寡核苷酸或对照物的大鼠接受前脑缺血和 Cornu ammonis（CA）1 神经元存活和蛋白质水平评估。前脑缺血增加了海马 CA1 区的 miR-181a 表达并降低了 Bcl-2 蛋白。miR-181a 反义寡核苷酸降低了 miR-181a 水平，减少了 CA1 神经元丢失，增加了 Bcl-2 蛋白，并显著防止了谷氨酸转运蛋白 1 的减少。因此，miR-181a 反义寡核苷酸减少了星形胶质细胞功能障碍的证据，并增加了 CA1 神经元的存活。因此，miR-181a 抑制可能是前脑或全脑缺血以及局灶性缺血的潜在靶点。
